Each cell contains hundreds of mitochondria and thousands of mitochondrial DNA (mtDNA) copies, which are maternally inherited. The mammalian mtDNA encodes 13 polypeptides that are essential for oxidative phosphorylation (OXPHOS) plus two rRNAs (12S and 16S) and 22 tRNAs that are required for mitochondrial protein synthesis. The mtDNA encoded polypeptide genes are structural subunits for four of the five OXPHOS enzyme complexes (I, III, IV and V). The nuclear DNA (nDNA) codes for all other mitochondrial proteins including all four subunits of complex II (succinate dehydrogenase), the mitochondrial DNA polymerase K subunits, the mitochondrial RNA polymerase components, the mitochondrial transcription factor (mtTFA), the mitochondrial ribosomal proteins and elongation factors, and the mitochondrial metabolic enzymes. Mitochondria generate energy via OXPHOS which “couples” electron transport with proton translocation for the production of ATP. Mitochondria are also the primary source of endogenous cellular ROS. The efficacy of mitochondrial energy and oxidant production is dependent upon a number of factors including local concentrations of both reactive nitrogen and oxygen species, mitochondrial antioxidants, cytokines, electron transport efficiency, metabolic reducing equivalent availability (NADH and FADH2), uncoupling protein (UCP) activities, and overall organelle integrity (damage to membranes, DNA, and proteins).